PMID- 24911002 OWN - NLM STAT- MEDLINE DCOM- 20150109 LR - 20140930 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 230 IP - 1 DP - 2015 Jan TI - A functional transient receptor potential vanilloid 4 (TRPV4) channel is expressed in human endothelial progenitor cells. PG - 95-104 LID - 10.1002/jcp.24686 [doi] AB - Endothelial progenitor cells (EPCs) are mobilized into circulation to replace damaged endothelial cells and recapitulate the vascular network of injured tissues. Intracellular Ca(2+) signals are key to EPC activation, but it is yet to be elucidated whether they are endowed with the same blend of Ca(2+) -permeable channels expressed by mature endothelial cells. For instance, endothelial colony forming cells (ECFCs), the only EPC subset truly committed to acquire a mature endothelial phenotype, lack canonical transient receptor potential channels 3, 5 and 6 (TRPC3, 5 and 6), which are widely distributed in vascular endothelium; on the other hand, they express a functional store-operated Ca(2+) entry (SOCE). The present study was undertaken to assess whether human circulating EPCs possess TRP vanilloid channel 4 (TRPV4), which plays a master signalling role in mature endothelium, by controlling both vascular remodelling and arterial pressure. We found that EPCs express both TRPV4 mRNA and protein. Moreover, both GSK1016790A (GSK) and phorbol myristate acetate and, two widely employed TRPV4 agonists, induced intracellular Ca(2+) signals uniquely in presence of extracellular Ca(2+). GSK- and PMA-induced Ca(2+) elevations were inhibited by RN-1734 and ruthenium red, which selectively target TRPV4 in mature endothelium. However, TRPV4 stimulation with GSK did not cause EPC proliferation, while the pharmacological blockade of TRPV4 only modestly affected EPC growth in the presence of a growth factor-enriched culture medium. Conversely, SOCE inhibition with BTP-2, La(3+) and Gd(3+) dramatically decreased cell proliferation. These data indicate that human circulating EPCs possess a functional TRPV4 protein before their engraftment into nascent vessels. CI - (c) 2014 Wiley Periodicals, Inc. FAU - Dragoni, Silvia AU - Dragoni S AD - Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy. FAU - Guerra, Germano AU - Guerra G FAU - Fiorio Pla, Alessandra AU - Fiorio Pla A FAU - Bertoni, Giuseppe AU - Bertoni G FAU - Rappa, Alessandra AU - Rappa A FAU - Poletto, Valentina AU - Poletto V FAU - Bottino, Cinzia AU - Bottino C FAU - Aronica, Adele AU - Aronica A FAU - Lodola, Francesco AU - Lodola F FAU - Cinelli, Maria Pia AU - Cinelli MP FAU - Laforenza, Umberto AU - Laforenza U FAU - Rosti, Vittorio AU - Rosti V FAU - Tanzi, Franco AU - Tanzi F FAU - Munaron, Luca AU - Munaron L FAU - Moccia, Francesco AU - Moccia F LA - eng PT - Journal Article PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (4-methyl-4'-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)-1,2,3-thiadiazole-5-carboxanilide) RN - 0 (Anilides) RN - 0 (Cation Transport Proteins) RN - 0 (N-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamide) RN - 0 (RN 1734) RN - 0 (RNA, Messenger) RN - 0 (Sulfonamides) RN - 0 (TRPV Cation Channels) RN - 0 (TRPV4 protein, human) RN - 0 (Thiadiazoles) RN - 11103-72-3 (Ruthenium Red) RN - GMW67QNF9C (Leucine) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - SY7Q814VUP (Calcium) SB - IM MH - Adult MH - Anilides/pharmacology MH - Calcium/metabolism MH - Cation Transport Proteins/biosynthesis MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Endothelial Cells/cytology/*metabolism MH - Endothelium, Vascular/*metabolism MH - Humans MH - Leucine/analogs & derivatives/pharmacology MH - Neovascularization, Physiologic/*physiology MH - RNA, Messenger/biosynthesis MH - Ruthenium Red/pharmacology MH - Stem Cells/cytology/*metabolism MH - Sulfonamides/pharmacology MH - TRPV Cation Channels/agonists/antagonists & inhibitors/*biosynthesis/genetics MH - Tetradecanoylphorbol Acetate/pharmacology MH - Thiadiazoles/pharmacology MH - Young Adult EDAT- 2014/06/10 06:00 MHDA- 2015/01/13 06:00 CRDT- 2014/06/10 06:00 PHST- 2014/03/31 00:00 [received] PHST- 2014/05/22 00:00 [accepted] PHST- 2014/06/10 06:00 [entrez] PHST- 2014/06/10 06:00 [pubmed] PHST- 2015/01/13 06:00 [medline] AID - 10.1002/jcp.24686 [doi] PST - ppublish SO - J Cell Physiol. 2015 Jan;230(1):95-104. doi: 10.1002/jcp.24686.